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Biomedical subjects

F Di Gregorio

Publications and source records attributed to F Di Gregorio.

At least 55 records · Page 3Linked to original sources
PubMed1995

Efficacy of an analysis of lymphocyte subsets in predicting the clinical response to alpha-interferon therapy in thalassaemia patients with chronic infection by hepatitis C virus: a pilot study.

alpha-interferon (alpha-IFN) has been used to treat chronic non-A non-B hepatitis in thalassaemic patients with response rates from 45% to 83%. Unfortunately, treatment with alpha-IFN is associated with side-effects which have a negative effect on the quality of life of the patient. Therefore it would be useful if we could distinguish in advance those patients who would benefit from such therapy from those who would not. In the present study we found that the modification of lymphocyte subsets 20 h after the administration of the first dose of alpha-IFN revealed that relative numbers of T helper lymphocytes (CD4+) increased in three non-responding patients and decreased in five responding patients, whereas those of T suppressor lymphocytes (CD8+), and natural killer cells (CD57+, CD16+) decreased in non-responding patients and increased in responding patients. Therefore analysis of the lymphocyte subsets CD4, CD8, CD57 and CD16 before and 20 h after the administration of alpha-IFN can be used to predict the clinical response to treatment with alpha-IFN.

Adolescent↗
PubMed1994

Immune status and immune response to diphtheria-tetanus and polio vaccines in allogeneic bone marrow-transplanted thalassemic patients.

We evaluated the immune status against diphtheria (D), tetanus (T) and polio viruses (PV) and the immune response to re-administration of the respective vaccines in a series of 23 transplanted homozygous beta-thalassemic patients, aged 5-17 years (mean age 12.1 +/- 3.1 years). They had been given compulsory DT toxoids and types 1, 2 and 3 PV vaccine in infancy and had been successfully submitted to allogeneic BMT 2-6 years previously. Prior to revaccination, a high percentage of subjects (from 48% for type 2 PV to 83% for D) had antibody levels below the protective levels and low geometric mean titers (GMTs). After revaccination (three doses of DT toxoids and of inactivated PV vaccine) the percentage of subjects with protective levels of antibodies rose to 86-100% and the GMTs increased markedly. We conclude that: (1) the protection afforded by compulsory DT and PV vaccines administered in infancy is almost entirely lost in beta-thalassemic patients for several years after BMT, (2) revaccination is necessary in these subjects, and (3) at least three doses of DT and PV vaccines must be administered to recover adequate protection.

Adolescent↗
PubMed1993

Febrile and afebrile convulsions: a clinical follow-up.

A joint study was performed on 204 children who suffered separate febrile (FS) and afebrile seizures (aFS) within a short space of time to evaluate the risk of subsequent convulsive crises. The data obtained revealed frequent recurrence of seizures and high risk of subsequent convulsive afebrile crises in these children.

Atrophy↗
PubMed1993

Histological findings and evidence of lipid conjugated dienes and malonyldialdehyde in human fetal aortas.

Recent evidence strongly suggests that peroxidative modification of lipids may play a significant role in atherogenesis. In our present research, we investigated if the oxidative stress mediated by oxygen free radicals was a pathophysiologic condition that occurred in the early stages of human development. Thus the aim of this research was to examine lipid peroxidation in human fetal aortas. Human fetal aortas and proximal iliac arteries (n = 8) were obtained from fetuses aged 7 +/- 2 months, immediately after autopsy. Lipids from the initial fatty streak lesions (LFS) and the vessels uninvolved (LUV) were extracted by the chloroform/methanol method. Lipid peroxidation levels were measured by two different methods: determination of lipid conjugate dienes (the spectrum trend was recorded from 320 to 200 nm with a spectrophotometer) and malonyldialdehyde (MDA) content (TBA method). We observed that lipid conjugated dienes were present in LFS, but not in LUV, with a characteristic absorption peak at 233 nm. In addition, MDA levels were significantly higher when the LFS = 3.85 +/- 0.91 nmol than when the LUV = 0.41 +/- 0.12 nmol (p < 0.001 versus LUV). The presence of lipid peroxidation in our samples could be mediated by free radical production in the first stages of human development. Thus these data suggest that LFS peroxidation mediated by free radicals occurs in the vascular circulation in the early stages of human development. This could influence the progression of vascular damage and atherosclerotic disease.

Aorta↗
PubMed1993

[Angiotensin II stimulates endothelin-1 release from human endothelial cells].

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide isolated from the culture supernatant of porcine aortic endothelial cells. This 21 amino-acid residue peptide has potent vasoconstrictive properties in vitro and in vivo. ET-1 action involves phosphatidylinositol turnover, calcium mobilization and protein kinase C activation. Endothelial cells have distinct receptors for different operating through hydrosoluble hormones. The aim of this study was to investigate on a possible role of angiotensin II (ANG II) to modulate the release ET-1 from human endothelial cells in vitro. These data revealed a time- and a dose-dependent increase of ET-1 production in response to ANG II. This mechanism may have important pathophysiological implications in vivo. In fact, a double-mechanism of secretion of ET-1 from endothelial cells could exist: one active in a physiological condition and an other in response to a vasoconstrictor stimuli (as well as ANG II). Furthermore, these results may suggest an additional favourable effect of ACE-inhibition in human hypertension therapy.

Angiotensin II↗
PubMed1991

Neopterin as a marker of C hepatitis in thalassaemia major.

The authors studied serum neopterin in 106 patients with beta thalassaemia major. A good correlation was found between neopterin values and glutamic pyruvic transaminase (GPT) mean values of the last 6 months, whereas no correlation was found between neopterin values and some siderosis indexes (iron/body weight, total accumulated iron). A statistically significant correlation was found between neopterin values (greater than 10 nM/L vs. less than 10 nM/L) and histological liver findings (chronic hepatitis vs. siderosis). Neopterin values were also statistically different between splenectomized and not splenectomized patients. Moreover serum neopterin was higher in HCV-Ab positive than in HCV-Ab negative patients, and 91.6% of the HCV-Ab positive group also showed histological signs of chronic hepatitis. These data suggest that increased serum neopterin might help to identify chronic C hepatitis in thalassaemic patients.

Adolescent↗
PubMed1991

A voltage- and time-dependent rectification in rat dorsal spinal root axons.

1. Rat dorsal spinal roots were studied by the use of whole-nerve sucrose gap and intra-axonal recording techniques. A prominent time-dependent conductance increase as evidenced by a relaxation or "sag" in membrane potential toward resting potential was elicited in dorsal spinal roots by constant hyperpolarizing current pulses. The relaxation, or sag, indicative of inward rectification, reached a maximal level and then decayed during the current pulse. 2. The time-dependent sag elicited by hyperpolarization was reduced when Na+ or K+ was removed from the normal bath solution but was abolished with the removal of both Na+ and K+. Tetrodotoxin (TTX), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) did not affect the depolarization sag, suggesting that conventional voltage-dependent sodium and potassium channels do not underlie the inward rectification. 3. Cs+ in low concentrations completely abolished the inward rectification, whereas Ba2+ induced a partial block. 4. Current-voltage curves indicate that the magnitude of the depolarizing sag increases monotonically with increasing hyperpolarization. The time required to reach peak hyperpolarization, maximal sag potential, and the time between peak hyperpolarization and sag membrane potentials decreases with increasing levels of hyperpolarization. 5. The inward rectification is refractory to further stimulation during its decay phase, as revealed by paired-pulse protocols. This decay in inward rectification is both time and voltage dependent and is observed on a single axon level by the use of intra-axonal recording techniques as well as from whole-root recordings in the sucrose gap. 6. It is concluded that rat dorsal root fibers display a prominent time-dependent conductance increase in response to hyperpolarization that depends on both Na+ and K+ permeability and is blocked by Cs+. This rectification displays a decay phase that has not been previously described for similar conductances. It is argued that the Na+ component of this conductance is primarily responsible for stabilizing membrane potential near resting potential during periods of hyperpolarization.

Animals↗
PubMed1991

[Clinico-pathological evaluation of patients with homozygous familial hypercholesterolemia].

The authors have studied 8 patients with Homozygous Familial Hypercholesterolemia (FHO) an autosomal genetic dominant disease due to mutation of the gene encoding a cell surface receptor for LDL. Anatomic and pathologic abnormalities caused by LDL-cholesterol and B-Apolipoprotein high plasma levels were found. We also measured malondialdehyde levels in plasma and atherosclerotic plaques of the only autoptic case observed. MDA-levels are an index of lipid peroxidation. Cutaneous xanthomatosis lesions and severe cardiovascular disease were also present.

Adult↗
PubMed1990

Efficacy of ganglioside treatment in reducing functional alterations induced by vincristine in rabbit peripheral nerves.

Vincristine (VCR) administration to rabbits resulted in severe electrophysiologic alterations of peripheral nerves. Sciatic nerve conduction velocity, compound action potential (CAP) amplitude, and area under the CAP waveform were all reduced in a dose-dependent fashion. In addition, the pattern of conduction velocity of both motor and sensory fibers was altered and shifted toward slow conduction classes. Simultaneous treatment with gangliosides limited significantly the changes in electrophysiologic parameters induced by VCR. It is suggested that gangliosides be given in the clinical setting as protection for the peripheral nerves against the side effects of antiblastic therapy.

Action Potentials↗
PubMed1990

Intradermal hepatitis B vaccination in thalassaemia.

Fifty six children with thalassaemia, and 118 healthy subjects, who had all been immunised with an intramuscular injection of hepatitis B vaccine (HB-VAX) into the deltoid area three years previously, were given booster doses intradermally. All responders (good = hepatitis B surface (HBs) antibody titre greater than or equal to 10 U/l; poor = HBs antibody titre less than 10 U/l) showed pronounced increase in anti-HBs titre, in many cases above 1000 U/l. We also found positive HBs antibody response after further doses (two to four) at intervals of 15 days in non-responders (those patients who formerly had shown no HBs antibody titre after the conventional schedule of vaccination). The humoral response was always preceded by a delayed tissue hypersensitivity reaction. In conclusion, vaccine against hepatitis B virus given in low doses intradermally produces an effective immune response; it is a useful method of enhancing the antibody response in exposed patients, and of vaccinating those who do not respond initially.

Antibody Formation↗
PubMed1989

Survival and causes of death in thalassaemia major.

Survival and causes of death were studied in 1087 Italian patients with thalassaemia major who were born on or after Jan 1, 1960. At the age of 15 years, the Kaplan-Meier estimate of survival after the first decade of life was 80.6% for subjects born in 1960-64, 84.2% for those born in 1965-69, and 96.9% for those born in 1970-74. At the age of 20 years, survival from the age of 10 was 59.1% for patients born in 1960-64, and 70.2% for those born in 1965-69; at 25 years, survival from the age of 10 was 40.7% in the 1960-64 cohort. Overall survival from birth for patients born in 1970-74 was 97.4% at 10 years, and 94.4% at 15 years. The most common cause of death was heart disease, followed by infection, liver disease, and malignancy.

Adolescent↗
PubMed1989

Functional evaluation of acute vincristine toxicity in rat skeletal muscle.

Vincristine sulfate (VCR) was administered intravenously to rats at doses of 0.25, 0.5, and 0.75 mg/kg. During the first week following VCR treatment, extensor digitorum longus (EDL) muscle contraction strength and fiber electrophysiologic parameters were measured. At all doses tested, VCR strongly reduced twitch and tetanic tension. EDL fiber resting membrane potential was affected in a dose-dependent manner, and membrane depolarization was associated with the loss of excitability. Local membrane hyperpolarization by intracellular current application restored the capacity to produce action potential (AP). However, to elicit APs with a normal rate of rise, polarizing current had to be maintained for 3-5 minutes, indicating that the removal of Na+ channel inactivation followed a slow kinetics. Minor alterations in spontaneous synaptic transmission and in evoked transmission during high-frequency repetitive stimulation were seen only at the highest dose. It is suggested that VCR impairs skeletal muscle function by affecting primarily the contractile apparatus, whereas sarcolemmal alterations are evident at increased doses of the drug.

Action Potentials↗
PubMed1989

Spontaneous and nerve-evoked quantal transmission in regenerated motor terminals.

Quantal acetylcholine release was studied in sciatic nerve-extensor digitorum longus muscle preparations from normal rats and in reinnervated muscles at different times following peroneus nerve crush. The efficiency of nerve-evoked transmission was regained almost completely at a time (20 days after crush) when the secretory response to increased extracellular K+ was very weak. This suggests that K+-induced secretion might be activated through mechanisms at least partially different from those involved in the response to nerve stimulation.

Animals↗
PubMed1988

Adaptation of sarcolemmal action potential mechanisms to chronic depolarization in denervated skeletal muscle.

Action potential properties were studied in rat extensor digitorum longus fibers, at different times after locally setting the membrane to a holding potential of -90 mV. Whereas in normal muscles holding potential duration had little effect on the action potential, the holding potential duration markedly influenced membrane excitability in the fibers previously depolarized by increasing the K+ concentration of the bathing medium. In this case, when the holding potential was prolonged from 20 to 180 s, action potential overshoot, maximum rate of rise, and maximum rate of fall increased 1.8-, 3.1-, and 1.8-fold, respectively. In the denervated muscle, overshoot and maximum rate of fall were dependent on the duration of holding potential application until denervation day 6, whereas maximum rate of rise was affected throughout the duration of this study (15 days of denervation). However, 180-s application of -90 mV holding potential elicited about a 2-fold increase of maximum rate of rise in the earlier denervation stages, and only a 1.5-fold increase at later times. These observations suggest that ultra-slow processes of Na+ conductance inactivation were less effective after 6 days of denervation. Correspondingly, extensor digitorum longus fibers acquired the ability to generate action potentials at a depolarized holding potential. The partial removal of ultra-slow Na+ inactivation after muscle denervation could substantially contribute to a general process of membrane adaptation, resulting in the capacity of voltage-dependent ion channels to operate in a condition of chronic depolarization.

Action Potentials↗